Identifying and characterizing the germinal genetic landscape of men with prostate cancer: A real-life, retrospective, multicenter study.

Germline variants in predisposition and DNA repair genes (BRCA1, BRCA2, ATM, NF1, MSH6) contributing to prostate cancer risk.

This real-life, retrospective, multicenter study assessed the germline testing landscape in men referred for genetic counselling because of prostate cancer, and the added benefit of next-generation sequencing (NGS) over founder variant testing alone. Of the 293 men tested, 39 (13.3%) had a positive result: 18 (6.1%) a variant in a high-penetrance gene (BRCA1, BRCA2, ATM, NF1, MSH6) and 21 (7.2%) a risk allele. One-third of the (likely) pathogenic variants identified by NGS were unique rather than founder variants. Family history of cancer was the only factor significantly associated with a positive result, and the authors conclude in favour of NGS irrespective of ethnicity and disease stage.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The practical message is clear: restricting testing to founder variants misses roughly one-third of causal variants in these patients, which argues for broad gene-wide analysis up front — in practice, exome sequencing interpreted against a relevant gene list. The main limitation is the selection bias inherent to a cohort referred for cancer genetic counselling, which probably inflates the 13.3% figure compared with an unselected prostate cancer population. It nonetheless provides a useful argument for widening germline testing indications in urology.

Analysis by Dr Thibaut Benquey